posted on 2021-04-02, 18:37authored byMarius
M. Kostelic, Ciara K. Zak, Hiruni S. Jayasekera, Michael T. Marty
Native mass spectrometry (MS) with
nanodiscs is a promising technique
for characterizing membrane protein and peptide interactions in lipid
bilayers. However, prior studies have used nanodiscs made of only
one or two lipids, which lack the complexity of a natural lipid bilayer.
To better model specific biological membranes, we developed model
mammalian, bacterial, and mitochondrial nanodiscs with up to four
different phospholipids. Careful selection of lipids with similar
masses that balance the fluidity and curvature enabled these complex
nanodiscs to be assembled and resolved with native MS. We then applied
this approach to characterize the specificity and incorporation of
LL-37, a human antimicrobial peptide, in single-lipid nanodiscs versus
model bacterial nanodiscs. Overall, development of these model membrane
nanodiscs reveals new insights into the assembly of complex nanodiscs
and provides a useful toolkit for studying membrane protein, peptide,
and lipid interactions in model biological membranes.